The cytotoxic and mutagenic properties of antitumor drugs such as adriamycin, acridines, diacridine, actinomycin D and Pt compounds are related to their interaction with nucleic acids and inhibition of protein synthesis. We have examined their interaction with human erythrocyte ghost membranes and murine mastocytoma cells using spin labeling techniques. These drugs induce changes in electron spin resonance of the spin labeled ghost membranes and in the mastocytoma cells. These findings suggest that these drugs induce changes in protein conformation of the membranes. Using cytofluorescence technique, we have shown that the binding of adriamycin leads to the protein aggregation in Hut-II cells. Thus, membrane binding properties of these drugs may be important in their mechanism of action.